crossing96/oncoscreening huggingface dataset:
Stereotactic Radiotherapy for Penile Metastasis: Case Report and Systematic Literature Review.	"INTRODUCTION: Penile metastases (PMs) are a rare clinical presentation mainly related to advanced stages of disease. Considering the low incidence, an optimal treatment approach has not yet been defined; surgery, chemotherapy, and radiotherapy (RT) are different options used in the vast majority with palliative intent. The advances in modern RT can represent an innovative tool in PM management and a curative option. This paper aimed to report the case of a PM patient treated with stereotactic body radiotherapy (SBRT) and perform a systematic literature review of current evidence on the RT approach to PM. CASE PRESENTATION: We reported the case of an 80-year-old patient with PM from primary bladder cancer. Following the surgical approach for the primary tumor, evidence of PM was shown, and the patient was admitted to SBRT treatment on PM after an adjuvant RT course on the pelvis. A 25 Gy in 5-fraction SBRT treatment was performed, and a complete clinical response was shown at the first follow-up. A PubMed/MEDLINE and Embase systematic review was carried out. The search strategy terms were [(""penile metastasis""/exp OR ""penile metastasis"" OR (penile AND (""metastasis""/exp OR metastasis))) AND (""radiotherapy""/exp OR radiotherapy)] and only original articles up to October 24, 2023 were considered. CONCLUSION: A total of 174 studies were obtained using the previously mentioned search strategy, and the analysis was performed on 15 papers obtained following the complete selection process. All reported evidence was focused on the palliative approach of PM, showing good results in terms of symptom control. The potential role of modern RT in the management of PM has yet to be defined. The reported case showed the feasibility and the clinical impact of SBRT in PM treatment."	bladder
Single-cell and bulk RNA-sequence identiﬁed ﬁbroblasts signature and CD8 + T-cell - ﬁbroblast subtype predicting prognosis and immune therapeutic response of bladder cancer, based on machine learning: bioinformatics multi-omics study.	BACKGROUND: Cancer-associated fibroblasts (CAFs) are found in primary and advanced tumours. They are primarily involved in tumour progression through complex mechanisms with other types of cells in the tumour microenvironment. However, essential fibroblasts-related genes (FRG) in bladder cancer still need to be explored, and there is a shortage of an ideal predictive model or molecular subtype for the progression and immune therapeutic assessment for bladder cancer, especially muscular-invasive bladder cancer based on the FRG. MATERIALS AND METHODS: CAF-related genes of bladder cancer were identified by analysing single-cell RNA sequence datasets, and bulk transcriptome datasets and gene signatures were used to characterize them. Then, 10 types of machine learning algorithms were utilised to determine the hallmark FRG and construct the FRG index (FRGI) and subtypes. Further molecular subtypes combined with CD8+ T-cells were established to predict the prognosis and immune therapy response. RESULTS: Fifty-four BLCA-related FRG were screened by large-scale scRNA-sequence datasets. The machine learning algorithm established a 3-genes FRGI. High FRGI represented a worse outcome. Then, FRGI combined clinical variables to construct a nomogram, which shows high predictive performance for the prognosis of bladder cancer. Furthermore, the BLCA datasets were separated into two subtypes - fibroblast hot and cold types. In five independent BLCA cohorts, the fibroblast hot type showed worse outcomes than the cold type. Multiple cancer-related hallmark pathways are distinctively enriched in these two types. In addition, high FRGI or fibroblast hot type shows a worse immune therapeutic response. Then, four subtypes called CD8-FRG subtypes were established under the combination of FRG signature and activity of CD8+ T-cells, which turned out to be effective in predicting the prognosis and immune therapeutic response of bladder cancer in multiple independent datasets. Pathway enrichment analysis, multiple gene signatures, and epigenetic alteration characterize the CD8-FRG subtypes and provide a potential combination strategy method against bladder cancer. CONCLUSIONS: In summary, the authors established a novel FRGI and CD8-FRG subtype by large-scale datasets and organised analyses, which could accurately predict clinical outcomes and immune therapeutic response of BLCA after surgery.	bladder
NCCN Guidelines® Insights: Bladder Cancer, Version 3.2024.	Bladder cancer, the sixth most common cancer in the United States, is most commonly of the urothelial carcinoma histologic subtype. The clinical spectrum of bladder cancer is divided into 3 categories that differ in prognosis, management, and therapeutic aims: (1) non-muscle-invasive bladder cancer (NMIBC); (2) muscle invasive, nonmetastatic disease; and (3) metastatic bladder cancer. These NCCN Guidelines Insights detail recent updates to the NCCN Guidelines for Bladder Cancer, including changes in the fifth edition of the WHO Classification of Tumours: Urinary and Male Genital Tumours and how the NCCN Guidelines aligned with these updates; new and emerging treatment options for bacillus Calmette-Guérin (BCG)-unresponsive NMIBC; and updates to systemic therapy recommendations for advanced or metastatic disease.	bladder
Nucleoporin 93 Regulates Cancer Cell Growth and Stemness in Bladder Cancer via Wnt/β-Catenin Signaling.	Bladder cancer (BLCA) is a prevalent cancer type with an unmet need for new therapeutic strategies. Nucleoporin 93 (Nup93) is implicated in the pathophysiology of several cancers, but its relationship with bladder cancer remains unclear. Nup93 expression was analyzed in TCGA datasets and 88 BLCA patient samples. Survival analysis and Cox regression models evaluated the association between Nup93 levels and patient prognosis. BLCA cells were used to investigate the effects of Nup93 overexpression or knockdown on cell growth, invasion, stemness (sphere formation and ALDH2 + cancer stem cell marker), and Wnt/β-catenin signaling in vitro. The Wnt activator BML-284 was used to confirm the involvement of Wnt/β-catenin signaling pathway. A xenograft mouse model validated the in vitro findings. Nup93 was highly expressed in BLCA tissues and cell lines, and high Nup93 expression correlated with poor prognosis in BLCA patients. Nup93 silencing inhibited BLCA cell proliferation, Wnt/β-catenin activation, and cancer cell stemness. Conversely, Nup93 overexpression promoted these effects. BML-284 partially rescued the reduction in cell growth and stemness markers caused by Nup93 knockdown. Nup93 knockdown also suppressed the tumor formation of BLCA cells in vivo. Nup93 regulates BLCA cell growth and stemness via the Wnt/β-catenin pathway, suggesting its potential as a prognostic marker and therapeutic target in BLCA.	bladder
Knockdown of iPLA(2)γ enhances cisplatin-induced apoptosis by increasing ROS-dependent peroxidation of mitochondrial phospholipids in bladder cancer cells.	Cisplatin (CDDP) is a platinum-based drug with anti-cancer activity and is widely used as a standard therapy for bladder cancer. It is well known that CDDP causes cell death by increasing the generation of reactive oxygen species (ROS) and lipid peroxidation, but the mechanism of its anti-cancer effects has not been fully elucidated. There are still some problems such as chemoresistance in CDDP therapy. In the present study, we found the expression of Ca(2+)-independent phospholipase A(2)γ (iPLA(2)γ), which has been reported to regulate cellular redox homeostasis by inhibiting lipid peroxide accumulation, in human bladder cancer tissues. Thus, we investigated the effect of iPLA(2)γ knockdown on CDDP-induced bladder cancer cell death. As a result, we found that iPLA(2)γ knockdown significantly enhanced CDDP-induced apoptosis, intracellular and mitochondrial ROS production, cytochrome c release and caspase activation in bladder cancer cells. Moreover, mitochondrial membrane potential was decreased and peroxidation of mitochondrial phospholipids was increased by iPLA(2)γ knockdown. It was also shown that co-treatment of bromoenol lactone, an iPLA(2) inhibitor, increased CDDP-induced apoptosis. These results indicated that iPLA(2)γ plays an important role in protecting bladder cancer cells from CDDP-induced apoptosis, and that iPLA(2)γ inhibitors might represent a novel strategy in CDDP-based multi-drug therapy.	bladder
The association between the human papillomavirus (HPV) and the diagnosis of bladder cancer: systematic review and meta-analysis.	BACKGROUND: Bladder cancer (BC) is the seventh most common cancer worldwide. Not every infection ends as cancer, although the HPV-induced carcinogenesis is a complex process consequence of inflammation. To determine the association between human papillomavirus (HPV) and the diagnosis of bladder cancer. METHODS: We carried out a systematic review according to Cochrane and PRISMA recommendations. We searched in EMBASE, Medline (Ovid), and The Cochrane Central Register of Controlled Trials (CENTRAL), from inception to nowadays. We included case-control studies. The risk of bias assessment was performed based on QUADAS2. We performed a random effect Meta-analysis. RESULTS: We included 14 studies in qualitative and quantitative analysis. There was mainly a low risk of bias. We finally found a strong association between the presence of HPV and bladder cancer diagnosis (OR 4.18 95%CI 2.63-6.66; I2 = 40%). CONCLUSIONS: HPV is currently associated with the diagnosis of bladder cancer.	bladder
Spatial Distribution of Macrophage and Lymphocyte Subtypes within Tumor Microenvironment to Predict Recurrence of Non-Muscle-Invasive Papillary Urothelial Carcinoma after BCG Immunotherapy.	Non-muscle-invasive papillary urothelial carcinoma (NMIPUC) of the urinary bladder is the most common type of bladder cancer. Intravesical Bacille Calmette-Guerin (BCG) immunotherapy is applied in patients with a high risk of recurrence and progression of NMIPUC to muscle-invasive disease. However, the tumor relapses in about 30% of patients despite the treatment, raising the need for better risk stratification. We explored the potential of spatial distributions of immune cell subtypes (CD20, CD11c, CD163, ICOS, and CD8) within the tumor microenvironment to predict NMIPUC recurrence following BCG immunotherapy. Based on analyses of digital whole-slide images, we assessed the densities of the immune cells in the epithelial-stromal interface zone compartments and their distribution, represented by an epithelial-stromal interface density ratio (IDR). While the densities of any cell type did not predict recurrence, a higher IDR of CD11c (HR: 0.0012, p-value = 0.0002), CD8 (HR: 0.0379, p-value = 0.005), and ICOS (HR: 0.0768, p-value = 0.0388) was associated with longer recurrence-free survival (RFS) based on the univariate Cox regression. The history of positive repeated TUR (re-TUR) (HR: 4.93, p-value = 0.0001) and T1 tumor stage (HR: 2.04, p-value = 0.0159) were associated with shorter RFS, while G3 tumor grade according to the 1973 WHO classification showed borderline significance (HR: 1.83, p-value = 0.0522). In a multivariate analysis, the two models with a concordance index exceeding 0.7 included the CD11c IDR in combination with either a history of positive re-TUR or tumor stage. We conclude that the CD11c IDR is the most informative predictor of NMIPUC recurrence after BCG immunotherapy. Our findings highlight the importance of assessment of the spatial distribution of immune cells in the tumor microenvironment.	bladder
Effects of androgen suppression therapy on the incidence and prognosis of bladder cancer: An updated systematic review and meta-analysis.	INTRODUCTION: The influence of androgen suppression therapy (AST) on bladder cancer (BCa) remains controversial, as recent studies have not reached a consensus regarding the relationship between AST and the incidence or prognosis of BCa. MATERIALS AND METHODS: We perform an updated systematic review and meta-analysis utilizing the most recent evidence to investigate the potential influence of AST on the incidence and prognosis of BCa. A comprehensive literature search was performed on the PubMed, Medline, Embase, Web of Science, and the Cochrane Library databases to include potentially eligible studies. Hazard ratios (HR) and odds ratios (OR) were used to calculate the incidence and prognosis of BCa. RESULTS: This meta-analysis included 22 studies with 700,755 participants which investigated the impact of AST on the risk and prognosis of BCa. The pooled results revealed no significant relation between AST and a decreased incidence of BCa (OR: 0.92, 95%CI: 0.77-1.09, P = 0.342). Subgroup analysis reported that patients receiving 5-alpha reductase inhibitors (5-ARIs) exhibited a significantly lower risk of BCa (OR: 0.83, 95%CI: 0.75-0.91, P < 0.001), while androgen deprivation therapy did not show a significant reduction (OR: 1.00, 95%CI: 0.46-2.16, P = 0.995). AST may also significantly improve the recurrence-free survival of patients with BCa (HR: 0.69, 95%CI: 0.50-0.95, P = 0.023). We also detected a significant improvement in OS among BCa patients who received 5-ARIs compared to those without 5-ARIs (HR: 0.82, 95%CI: 0.68-0.99, P = 0.037). CONCLUSION: No significant correlation was found between AST and a decreased BCa incidence, while 5-ARIs have demonstrated efficacy in reducing BCa occurrence. Moreover, patients who received AST demonstrated improved prognosis.	bladder
CRISPR-based gene expression platform for precise regulation of bladder cancer.	The development of compact CRISPR systems has facilitated delivery but has concurrently reduced gene editing efficiency, thereby limiting the further utilization of CRISPR systems. Enhancing the efficiency of CRISPR systems poses a challenging task and holds significant implications for the advancement of biotechnology. In our work, we report a synthetic dual-antibody system that can stably exist in the intracellular environment, specifically inhibiting the functions of NF-κB and β-catenin. This not only elevates the transgenic expression of the CRISPR system by suppressing the innate immune response within cells to enhance the gene editing efficiency but also demonstrates a notable tumor inhibitory effect. Based on the specific output expression regulation of CRISPR-CasΦ, we constructed a CRISPR-based gene expression platform, which includes sensor modules for detecting intracellular β-catenin and NF-κB, as well as an SDA module to enhance overall efficiency. In vitro experiments revealed that the CRISPR-based gene expression platform exhibited superior CDK5 expression inhibition efficiency and specific cytotoxicity towards tumor cells. In vitro experiments, we found that CRISPR-based gene expression platforms can selectively kill bladder cancer cells through T cell-mediated cytotoxicity. Our design holds significant assistant potential of transgene therapy and may offer the capability to treat other diseases requiring transgene therapy.	bladder
Nivolumab + Ipilimumab as Immunotherapeutic Boost in Metastatic Urothelial Carcinoma: A Nonrandomized Clinical Trial.	IMPORTANCE: Studies with nivolumab, an approved therapy for metastatic urothelial carcinoma (mUC) after platinum-based chemotherapy, demonstrate improved outcomes with added high-dose ipilimumab. OBJECTIVE: To assess efficacy and safety of a tailored approach using nivolumab + ipilimumab as an immunotherapeutic boost for mUC. DESIGN, SETTING, AND PARTICIPANTS: In this phase 2 nonrandomized trial, patients with mUC composed 2 cohorts. Cohort 1 received first-line or second-/third-line nivolumab with escalating doses of ipilimumab, and cohort 2 received second-/third-line nivolumab with high-dose ipilimumab. Recruitment spanned 26 sites in Germany and Austria from August 8, 2017, to February 18, 2021. All patients had a 70% or higher Karnofsky Performance Score and measurable disease per Response Evaluation Criteria in Solid Tumours, version 1.1. INTERVENTIONS: All patients initiated 4 doses of 240-mg nivolumab (1× every 2 wk). Week 8 nonresponders received nivolumab + ipilimumab (1× every 3 wk). Cohort 1 received 2 doses of 3-mg/kg nivolumab + 1-mg/kg ipilimumab followed by 2 doses of 1-mg/kg nivolumab + 3-mg/kg ipilimumab if no response. Due to safety concerns, cohort 1 treatment was halted, and first-line cohort 2 treatment was not pursued. Cohort 2 received 2 to 4 doses of 1-mg/kg nivolumab + 3-mg/kg ipilimumab. Responders continued with nivolumab maintenance but could receive nivolumab + ipilimumab for later progression. MAIN OUTCOMES AND MEASURES: The primary end point was objective response rate. RESULTS: The study comprised 169 patients (118 [69.8%] men; median [range] age, 68 [37-84] years): 86 in cohort 1 (42 first-line; 44 second-/third-line) and 83 in cohort 2. The median (IQR) follow-up times were 10.4 (4.2-23.5) months (first-line cohort 1), 7.5 (3.1-23.8) months (second-/third-line cohort 1), and 6.2 (3.2-22.7) months (cohort 2). Response rates to nivolumab induction were 12/42 (29%, first-line cohort 1), 10/44 (23%, second-/third-line cohort 1), and 17/83 (20%, cohort 2). Response rates to a tailored approach were 20/42 (48% [90% CI, 34%-61%], first-line cohort 1), 12/44 (27% [90% CI, 17%-40%], second-/third-line cohort 1), and 27/83 (33% [90% CI, 23%-42%], cohort 2). Three-year overall survival rates for first-line cohort 1, second-/third-line cohort 1, and cohort 2 using the Kaplan-Meier method were 32% (95% CI, 17%-49%), 19% (95% CI, 8%-33%), and 34% (95% CI, 23%-44%), respectively. CONCLUSIONS AND RELEVANCE: In this nonrandomized trial, although first-line cohort 1 treatment improved objective response rates, considerable progression events urge caution with this as a first-line therapy. Second-/third-line cohort 1 treatment did not improve response rates compared with nivolumab monotherapy. However, added high-dose ipilimumab may improve tumor response and survival in patients with mUC. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT03219775.	bladder
Pre-first-line chemotherapy risk stratification for overall survival in advanced urothelial carcinoma in sequential therapy era.	PURPOSE: To explore pre-treatment risk factors for overall survival (OS) in advanced urothelial carcinoma (UC) patients treated with first-line (1L) chemotherapy in sequential therapy (ST) era. Additionally, to evaluate the proportion of patients who were not able to undergo subsequent immune checkpoint inhibitor (ICI) therapy according to the subgroups stratified by the risk factors. METHODS: A multicenter retrospective study was conducted. Metastatic or locally advanced UC patients treated between 2017 and 2022 were included. The Kaplan-Meier method with the log-rank test and multivariate Cox regression models were used to address OS. RESULTS: Three hundred and fourteen patients treated with 1L chemotherapy were included in the study and 57 (18.2%) patients were not able to proceed to subsequent ICI therapy. Pre-chemotherapy risk factors for OS in 314 patients were ECOG-PS 1 or more, having no primary site resection, C-reactive protein (CRP) level of 3 mg/dL or more, and non-cisplatin-based regimen. Patients having 3 or 4 risk factors had higher risk for not being able to receive ST (Mann-Whitney U test, P < 0.001). As risk factors for OS in 230 patients who were able to receive ST, having no primary site resection, a neutrophil to lymphocyte ratio of 3 or more, and the presence of liver metastasis were identified. CONCLUSION: We reported the risk factors for OS in advanced UC patients treated with 1L chemotherapy in ST era. Patients with high risk for OS may not be able to proceed to subsequent ICI therapy even in the ST era.	bladder
Evaluation of magnetic resonance imaging for bladder cancer detection following transurethral resection of bladder tumour (TURBT).	PURPOSE: To evaluate the performance of MRI for detection of bladder cancer following transurethral resection of bladder tumour (TURBT). METHODS: This single-centre retrospective study included forty-one consecutive patients with bladder cancer who underwent bladder MRI after TURBT. Two uroradiologists retrospectively assessed the presence of tumour using bladder MRI with and without DWI (diffusion weighted imaging) using a five-point Likert scale. Sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV) were calculated and inter-reader agreement was assessed. Histopathology was used as the reference standard. RESULTS: 24 out of 41 patients (58.5%) had no residual tumour or Tis (carcinoma in situ) after TURBT. Sensitivity, specificity, PPV and NPV for detection of tumour using T1WI (T1-weighted imaging) and T2WI (T2-weighted imaging) was 50.0%, 54.6%, 21.1%, and 81.8%, respectively and for T1WI, T2WI and DWI combined was 100%, 76.5%, 50.0% and 100%, respectively. Overestimation of tumour was more common than underestimation. MRI showed high accuracy for patients in whom there was no residual tumour (78.9%). Inter-reader agreement for tumour detection improved from fair (κ = 0.54) to moderate (κ = 0.70) when DWI was included. CONCLUSION: Non-contrast MRI with DWI showed high sensitivity and relatively high specificity for detection of residual tumour after TURBT. Inter-reader agreement improved from fair to moderate with the addition of DWI. MRI can be useful after TURBT in order to guide further management.	bladder
Improving detection of carcinoma in situ in bladder cancer: urinary cytology vs the Xpert® BC Monitor.	OBJECTIVE: To investigate and compare the performance of urinary cytology and the Xpert BC Monitor test in the detection of bladder cancer in various clinically significant patient cohorts, including patients with carcinoma in situ (CIS), in a prospective multicentre setting, aiming to identify potential applications in clinical practice. PATIENTS AND METHODS: A total of 756 patients scheduled for transurethral resection of bladder tumour (TURBT) were prospectively screened between July 2018 and December 2020 at six German University Centres. Central urinary cytology and Xpert BC Monitor tests were performed prior to TURBT. The diagnostic performance of urinary cytology and the Xpert BC Monitor was evaluated according to sensitivity (SN), specificity (SC), negative predictive value (NPV) and positive predictive value (PPV). Statistical comparison of urinary cytology and the Xpert BC Monitor was conducted using the McNemar test. RESULTS: Of 756 screened patients, 733 (568 male [78%]; median [interquartile range] age 72 [62-79] years) were included. Bladder cancer was present in 482 patients (65.8%) with 258 (53.5%) high-grade tumours. Overall SN, SC, NPV and PPV were 39%, 93%, 44% and 92% for urinary cytology, and 75%, 69%, 59% and 82% for the Xpert BC Monitor. In patients with CIS (concomitant or solitary), SN, SC, NPV and PPV were 59%, 93%, 87% and 50% for urinary cytology, and 90%, 69%, 95% and 50% for the Xpert BC Monitor. The Xpert BC Monitor missed four tumours (NPV = 98%) in patients with solitary CIS, while potentially avoiding 63.3% of TURBTs in inconclusive or negative cystoscopy and a negative Xpert result. CONCLUSION: Positive urinary cytology may indicate bladder cancer and should be taken seriously. The Xpert BC Monitor may represent a useful diagnostic tool for correctly identifying patients with solitary CIS and unsuspicious or inconclusive cystoscopy.	bladder